Book Volume 5
Preface
Page: i-i (1)
Author: Rupesh K. Gautam, Lokesh Deb and Kamal Dua
DOI: 10.2174/9789815050776122010001
Rheumatoid Arthritis: Introduction
Page: 1-25 (25)
Author: Diptendu Bhowmik, Venu Kola, Subba Rao Chamakuri and Chiranjib Bhattacharjee*
DOI: 10.2174/9789815050776122010003
PDF Price: $15
Abstract
Rheumatoid Arthritis elaborated as Rheumatoid Arthritis is a systemic
chronic inflammatory condition that might affect numerous organs and tissues in a
human body, but mainly it attacks the synovial joints. These methods result in the
inflammatory synovitis (synovium) response. Factors that lead to an increase in the risk
of rheumatoid arthritis are age, sex, family history, smoking, obesity, and exposure to
pollutants. RA holds the ability to put a person at a higher risk of developing other
medical conditions if it is not controlled timely. A syndrome named carpal tunnel is
another common condition found in people suffering from rheumatoid arthritis.
Trauma, infection, smoking cigarettes are some of the examples of external triggers
which can trigger the reaction of the auto-immune system, which results in chronic
joint inflammation and synovial hypertrophy in addition to a potential of other
manifestations, which will be theorized for going on in people prone genetically. The
pathological process of the disease usually results in destructing the articular cartilage
as well as the joints ankylosis. Rheumatoid Arthritis could also result in diffusive lung
inflammation, sclera, pleura, pericardium, as well as nodular lesions, which are also
common in subcutaneous tissue. However, the causes of RA are still not known, the
autoimmunity holds an important part in both the progression and chronicity.
Rheumatoid Arthritis is a systemic disorder. RA can be prevented by using coldwater,
living fish oil, from the herring, cod, mackerel, and salmon fish, which contains
omega-3 fatty acids in high amounts, Vitamin-D supplements, and adopting the
lifestyle modifications such as avoiding smokingand weight loss.
Conventional Therapy for Rheumatoid Arthritis
Page: 26-49 (24)
Author: Anil T. Pawar, Akshay M. Baheti*, Pallavi Adate-More and Aman Upaganlawar
DOI: 10.2174/9789815050776122010004
PDF Price: $15
Abstract
Rheumatoid arthritis (RA) is a chronic disorder characterized by
inflammation of the synovial membrane of peripheral joints, which may lead to
progressive functional impairment. The small joints of hands and feet commonly
involved in RA often irregularly cause pain, stiffness, and malfunction of the joints.
Treatment of rheumatoid arthritis is a multidisciplinary approach that aims to mitigate
pain and inflammation, restore joint functions, and maintain day-to-day operations. In
realistic terms, inhibition of inflammation is the target of intensive therapy. This could
be frequently achieved with two main classes of medications, namely non-steroidal
anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs
(DMARDs). NSAIDs and glucocorticoids are suggested for use in the preliminary
stages of RA for short-term and symptomatic pain relief. Glucocorticoids are also
recommended in patients awaiting a response to DMARD therapy. DMARDs are
categorized into conventional or biological types. Biologic DMARDs are highly
specific and target a specific pathway of the immune system. This chapter is an attempt
to review the traditional therapies which are used in the management and treatment of
RA.
Role of Biomarkers in Rheumatoid Arthritis
Page: 50-71 (22)
Author: Hitesh Malhotra* and Anjoo Kamboj
DOI: 10.2174/9789815050776122010005
PDF Price: $15
Abstract
Rheumatoid arthritis is a chronic inflammatory condition that mainly affects
the joint due to hyperactive immune reactions. The disease involves each component of
the joint tissue with varying degrees of inflammation and destruction. The basic
pathogenesis includes two key points, i.e., hyperactive immune reaction and
inflammation. The phenomenon is driven by biomolecules which form a complex
pathophysiological network, resulting in disease development and progression. The
biomolecules like cytokines, such as interleukins, tumor necrosis factor-alpha, and
interferon, play a fundamental role in joint and cartilage destruction, production of
destructive enzymes, inflammatory reaction, and comorbidities related to the disease.
From various pre-clinical and clinical researches, various attributes of disease
development and progression can be demonstrated by focusing on the biological
contribution of mediators, like IL-1, TNF- α, IL-6, IL-15, IL-17, and IL-18. Numerous
reports confer the successful treatment of RA that might be possible by blocking the
activity of these biomarkers. In this chapter, we discuss the role of biomolecules in the
pathology of arthritis.
Bioactive Compounds in Rheumatoid Arthritis
Page: 72-96 (25)
Author: Sudha Vengurlekar* and Subhash Chandra Chaturvedi
DOI: 10.2174/9789815050776122010006
PDF Price: $15
Abstract
Rheumatoid arthritis is a severe systemic autoimmune disorder with limited
option available for treatment and no curative therapy available at present. Rheumatoid
arthritis manifests clinically through polyarthralgia related to joint dysfunction, which
triggers the autoimmune responses associated with antibodies against the selfneoepitopes and causes the chronic arthritic attack. Bone destruction is an important
feature to understand the pathology of rheumatoid arthritis, which may lead to a serious
concern for the patient for living a quality life. Available drugs for rheumatoid arthritis
such as methotrexate, hydroxychloroquine, and sulfasalazine exert effects on bone
metabolism in immune cells and cytokines that result in relieving pain, improving the
quality of life but still, the chronic teratogenic and toxic effects are challenging in
management of anti-arthritic drugs. This chapter reviews the current trend of bioactive
compounds for the treatment of rheumatoid arthritis, which may lead to the
development of novel anti-rheumatoid arthritis agents.
Traditional Medicinal Plants: Safe and Efficacious Potential Drugs in the Management of Rheumatoid Arthritis
Page: 97-117 (21)
Author: Sarath Nalla*, Sahdeo Prasad, Lakshmi Kavuri and Vijetha Pendyala
DOI: 10.2174/9789815050776122010007
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Abstract
Rheumatoid Arthritis is an autoimmune, chronic inflammatory disorder that
affects the synovial tissues of the joints. Whilst the standard treatment regimen
involves non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic
agents and glucocorticoids attenuate the symptoms. However, the long-standing use of
all these drugs causes adverse effects, which leads to the research on medicinal plants.
History shows that many medicinal plants are an integral part of various traditional
medicine systems, thus facilitating an alternative form of therapy in various parts of the
world. Since ancient civilization, many of the medicinal plants that used as popular
remedies are available abundantly in Asia. In this chapter, we are presenting the
information on various medicinal plants found in Asia that are reported to be having
anti-arthritic activity. Scientific studies revealed that herbs exert beneficial effects in
treating arthritis by numerous cellular mechanisms, including downregulation of proinflammatory cytokines like TNF-α, IL-6, and NF-κB, oxidative stress suppression,
suppression of cartilage degradation with degradative metalloproteinases, and
increasing antioxidant performance. A variety of phytoconstituents from diverse
chemical categories such as flavonoids, lignans, coumarins, terpenes, glycosides,
phytoestrogens, sesquiterpene lactones, anthraquinones, alkaloids, and thymoquinone
are extracted from these medicinal plants. Additionally, in this chapter, the
pharmacological actions of these plants were also discussed.
Inflammatory Mediators and Cytokines involved in Rheumatoid Arthritis
Page: 118-134 (17)
Author: Vikash Sharma, Shiv Shankar Shukla, Amber Vyas and Ravindra Kumar Pandey*
DOI: 10.2174/9789815050776122010008
PDF Price: $15
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease that mostly
affects the joints. Inflammation is an immune response of the human body, but an
overabundance of such responses is thought to be a key element in the evolution of
many other issues, including RA, cancer, and neurological illnesses. The growth and
inhibition of RA necessitate the identification of a precise mechanism and target in the
body. Interleukins (IL), tumour necrosis factors (TNF-), interferons (INF), and
arachidonic acid derivatives are the most important cytokines and inflammatory
mediators in rheumatoid arthritis. IL-6 inhibitors, JAK inhibitors, anti-TNF, and
currently available disease-modifying anti-rheumatic medications (DMARDs) have all
been demonstrated to be effective in the treatment of RA. We have also summarised
the inflammatory mediators such as arachidonic acid metabolites and their role in
inflammation. This chapter also observed cytokines and other transcription factors that
play a role in the disease's onset and progression. The current study includes a wide
range of issues, including RA molecular pharmacology, such as cytokines
pharmacology, transcription factors, and other active biomolecules. However, the study
shows that a number of biomolecules and mediators play a key role in the pathogenesis
of RA, and a thorough understanding of the underlying pathways can aid in the creation
of new targeted pharmacological therapies that are both safer and more effective in RA.
Natural Products Targeting Various Mediators in Rheumatoid Arthritis
Page: 135-163 (29)
Author: Disha Arora*, Sanjay Sharma and Sumeet Gupta
DOI: 10.2174/9789815050776122010009
PDF Price: $15
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to an
inflammatory reaction, primarily affecting synovial joints and progressive cartilage and
bone destruction resulting in gradual joint immobility. Possibly, a diversity of
pharmacological intercessions are employed for treating arthritis. But modern treatment
is linked with serious adverse outcomes and high expenses. Therefore, alternative
therapies have been under examination. Scientific facts on RA have revealed that
conventional therapy offers a favourable impact by various actions (cellular) like
repression of oxidative stress, down-regulation of pro-inflammatory cytokines, such as
IL-6, NF-ƙB, and TNF-α, and inhibiting cartilage degradation. A wide range of active
phytoconstituents from the medicinal plants, such as terpenes, anthraquinones,
glycosylflavons, flavonols, dihydroflavonols, lignans, coumarins, phytoestrogens,
sesquiterpene lactones, thymoquinone, and alkaloids reduced the arthritic
manifestations through selecting the pro-inflammatory indicators, which play a role in
the pathogeny of the disease (RA). With numerous developments in the last few years
regarding functional studies or characterization of plant materials, the phase is put
down for extensive scientific trials or using the plants or their products to manage
rheumatoid arthritis. The chapter discusses the plants used conventionally with
phytoconstituents having anti-inflammatory action. This, in turn, leads to the
innovation of new benefits from natural products in the future.
Herbal Formulations Useful in the Treatment of Rheumatoid Arthritis
Page: 164-192 (29)
Author: Akshay M. Baheti, Anil T. Pawar* and Aman Upaganlawar
DOI: 10.2174/9789815050776122010010
PDF Price: $15
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of
joints. About 1% of the world's adult population is affected by RA. The commonly
used medications for RA are anti-inflammatory and disease-modifying agents. These
drugs revise the pathology and restore the quality of life but fail to completely cure the
disease. Furthermore, they cause various side effects such as gastrointestinal disorders,
cardiovascular toxicity, immunodeficiency, and irreversible organ damage. This has led
to greater global interest in herbal medicines due to better tolerance and minimum side
effects than synthetic drugs. These herbs are used in traditional forms like vatika,
gutika, medicated oils, medicated ghee, or in different modern formulations such as
tablets, capsules, gels and ointments. A large segment of RA patients has started
adopting herbal formulations and traditional systems of medicines; there is a need to
compile the data on herbal formulations used in RA management. This chapter will
attempt to review herbal formulations of various systems of medicines used for
rheumatoid arthritis.
Preclinical and Clinical Studies on Natural Products Used in Rheumatoid Arthritis
Page: 193-217 (25)
Author: Anil Kamboj and Randhir Singh*
DOI: 10.2174/9789815050776122010012
PDF Price: $15
Abstract
Rheumatoid Arthritis (RA) is a chronic autoimmune disease with unknown
etiology, characterized by progressive cartilage erosion leading to joint distortion and
polyarthritis. Rheumatoid arthritis significantly affects the quality of life.
Approximately 1% population of the world suffer from rheumatoid arthritis, and
prevalence of RA is increasing day by day. There are many synthetic compounds
available for the management and treatment of rheumatoid arthritis but,- these
therapeutic agents have significant side effects like diarrhea, rashes, alopecia,
stomatitis, infrequent myelosuppression, hepatotoxicity and other toxicities. Moreover,
symptoms can reappear after discontinuation of the therapy. Because of these side
effects, and limitations of the existing synthetic drug, patients are shifting their interest
from synthetic to natural products for the treatment well as management of rheumatoid
arthritis.This chapter gives an overview of several plants having medicinal properties
with a potent therapeutic value that can be used for the management of rheumatoid
arthritis.
Phytochemicals: A New Approach for Targeting Biomarkers in the Management of Arthritis
Page: 218-242 (25)
Author: Hitesh Malhotra*, Anjoo Kamboj and Peeyush Kaushik
DOI: 10.2174/9789815050776122010013
PDF Price: $15
Abstract
Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that
involves the destruction of bone as well as cartilage architecture and induces extensive
joint pain, stiffness and swelling. The condition is characterized by the infiltration of
inflammatory cytokines, such as IL-1, TNF-α, which results in synovial hyperplasia
and pannus formation. Currently, no effective curative treatment is available for RA
patients and the existing ones produce numerous unwanted effects. So,
phytoconstituents have been considered as a potential source for many such chronic
conditions with minimal side effects. Phytomolecules such as Andrographolide,
Berberine, Curcumin, Ginsenoside, Hesperidin, Kirenol, Madecassocide and various
other polyphenolic compounds are under clinical or pre-clinical trials for their antiarthritic efficacy. Phytochemicals used in the treatment of arthritis target the
inflammatory signaling pathway and hyperactive immune reactions. The compounds,
in addition to anti-inflammatory activity, also suppress bone erosion and osteoclastic
activity. Furthermore, phytomolecules inhibit the release and generation of reactive
oxygen species and proinflammatory cytokines.
Potential Biomolecules from the Natural Sources for the Treatment of Rheumatoid Arthritis: A Detailed Review
Page: 243-262 (20)
Author: Ajeya Samanta, Dhruba Bhattacharya, Kamalika Mazumder, Shreyans Kumar Jain and Kaushik Biswas*
DOI: 10.2174/9789815050776122010014
PDF Price: $15
Abstract
Rheumatoid arthritis is a disease of the immune system where proinflammatory mediators produce inflammation, swelling, and pain in joints and
muscles. Continuous progression may cause damage to articular cartilages, joint tissue,
and decaying of bones, which may ultimately lead to disability or mortality. Prevention
of the progression of rheumatoid arthritis is a severe challenge for the medical system
and scientific community. The present pharmaceutical intervention comprises
NSAIDS, steroids, and disease-modifying anti-arthritic drugs (DMARDs). Medical
interventions, like surgery and knee replacement, are also available. These synthetic
drugs are accompanied by several adverse effects ranging from acute to chronic ones.
The use of natural products is an important alternative for the treatment of rheumatoid
arthritis. Plants, microbes, and other natural sources involve vital bioactive molecules,
which are being employed in the treatment of several diseases. Plant-derived bioactive
molecules, like boswellic acid, acetyl-β-boswellic acid, guggulsterone, curcuminoids,
etc., are promising components, serving as a therapy for rheumatoid arthritis. These
bioactive molecules have been evaluated for their effects on rheumatoid arthritis using
different screening methods, and they have shown prospective results. Many plant
extracts have been used to halt the disease progression, and promising results have
been recorded. Bioactive molecules produced by microorganisms are potential
candidates to be used in rheumatoid arthritis, and few microorganisms could be used
directly as probiotics to combat the altered immune system. These microbes secrete
numerous chemicals into the gut of the host, which are responsible for inhibiting the
pro-inflammatory mediators, and helping to prevent the disease.
Introduction
Rheumatoid arthritis (RA) is the most common inflammatory complication and affects approximately 1 % of the global population. It affects three times more women than men. RA is an autoimmune disorder elicited by exposure of genetic factors from the host to unknown antigens causing arthritogenic complaints. It also includes the activation of lymphocytes as well as CD4+ helper T cells along with the local release of chronic inflammatory mediators and cytokines like tumor necrosis factor (TNF-α) and various cytokines like interleukins (IL) that enormously affect the joints. The available allopathic therapies for RA are not a cure for the complications, and antibody therapy and surgical procedures are expensive. However, in the present era, researchers and healthcare professionals have moved toward natural medicines obtained from plants and other natural sources. Research-based on developments in phytomedicine has progressed steadily. Evidence has been collected to show the massive therapeutic potential of medicinal plants used in various traditional systems against many pathological complications. Researchers have focused on the therapeutic potential of natural products used for treatment and counteracting various disorders along with their complications having negligible adverse effects. Natural Products for the Management of Arthritic Disorders compiles current knowledge about the bioactive compounds and herbal formulations useful in the treatment of rheumatoid arthritis. 11 chapters explain the role of natural products in the management of rheumatoid arthritis. Topics have been contributed by experts in medicinal chemistry and rheumatology. The book first introduces the reader to rheumatoid arthritis before delving into conventional and alternative therapies for the disease. The editors have also included special topics such as the biomarkers for RA, cytokines and anti-inflammatory mediators, and preclinical and clinical studies. The range of topics should provide a comprehensive overview of natural remedies for arthritis and the role of natural products in anti-arthritic drug development. The information will be useful for many readers including medical and pharmacology students, multidisciplinary research scholars, scientists, pharma/herbal/food industrialists, and policy makers.