Medicinal Plants Used for Treatment of Rheumatoid Arthritis : A

The objective of this present review is to evaluate the therapeutic potential of Zingiber officinale in rheumatoid arthritis. We have also aimed to present a summary of mechanism of action of specific phytochemicals of Zingiber officinale to reduce the pain claimed by RA-affected patients. Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease, which affects synovial tissue in multiple joints. Although conventional treatments of RA commonly alleviate the symptoms, high incidence of adverse reactions leads to research tendency towards complementary and alternative medicine. As various medicinal plants are traditionally used for the management of symptomatologies associated with RA in Persian medicine, we reviewed medicinal literature to confirm their efficacy in the management of RA. Key findings Scientific evidence revealed that traditional medicaments exert beneficial effects on RA through several cellular mechanisms including downregulation of pro-inflammatory cytokines such as TNF-a, IL-6 and NF-jB, suppression of oxidative stress, inhibition of cartilage degradation with destructive metalloproteinases and enhancement of antioxidant performance. Various active constituents from different chemical categories including flavonols, lignans, coumarins, terpenes, glycosylflavons, dihydroflavonols, phytoestrogens, sesquiterpene lactones, anthraquinones, alkaloids and thymoquinones have been isolated from the medicinal plants. Keyword: A review, Medicinal plants, rheumatoid, Genetic factors, Infectious agents. INTRODUCTION Rheumatoid Arthritis (RA) is a common autoimmune disease that is associated with progressive disability, systemic complications, early death, and socioeconomic costs. According to Data Monitor, RA affects approximately 1.8 million people in the U.S. and has no known cause. RA is not associated with factors such as aging. RA occurs when the body’s immune system malfunctions, attacking healthy tissue and causing inflammation, which leads to pain and swelling in the joints, and may eventually cause permanent joint damage and painful disability. The primary symptoms of RA include progressive immobility and pain, especially in the morning, with long-term sufferers experiencing continual joint destruction for the remainder of their lives. There is no known cure for RA. Once the disease is diagnosed, treatment is prescribed to alleviate symptoms and/or to slow or stop disease progression. RA is associated with a heavy burden on society in terms of disability and health and economic costs. Because RA tends to be progressive in nature, involving a worsening of symptoms over time, and often begins for many people during the early or middle years of life, the disease often has a long-term impact on functioning (over 30 years for many individuals), which translates to a considerable social and economic cost. For many patients, the chronic fatigue and pain associated with RA interferes significantly with the ability to function normally. Consequently, RA may take away a person’s ability to work. One study estimated that as many as one-third of people with RA are forced to stop working within 10 years of being diagnosed. This makes loss of productivity an important part of the overall burden of the disease. Additionally, the many health complications associated with RA make the disease expensive from a cost standpoint and can have a pronounced negative impact on quality of life. Fortunately, improvements in diagnosis and treatment of RA have meant that the impact of the disease on functioning and quality of life can be lessened. It is important to keep in mind that many of the studies that measure the impact of RA were conducted before some of the important recent treatment advances and don’t reflect the potential for the latest treatments to improve functioning. Many RA patients, who only decades ago would have lost the ability to work and care for themselves, with newer treatments are able to continue to work and lead full lives. Healthcare costs associated with RA are quite high. Based on American College of Rheumatology estimates, there are a quarter of a million hospital admissions and 9 million doctor visits annually in the US due to RA. The annual cost of care for a patient with RA in the US averages Mohanad et al. / Medicinal Plants Used... IJPCR, Volume 8, Issue 12: December 2016 Page 1686 almost $6,000 in direct costs related to RA (not including pharmaceutical costs) and another $2500 in costs not related to RA. One half of all health costs for RA are related to hospital admissions. The higher the disability associated with RA, the higher the health cost. For example, in one study that rated disability using the Health Assessment Questionnaire, patients who had a score of 3 on the questionnaire (this indicates a high level of disability) also had about 3 times the cost in terms of health services compared with patients who had a score of 1, which indicates a lower level of disability. This statistic emphasizes the importance of aggressive treatment to prevent or delay the disability that can be caused by RA. RA can cause economic burden, where it can severely restrict a person’s ability to carry out tasks related to work and may even force an individual to reduce the amount they work or make changes in employment to accommodate their disability. In some cases, where the disease is severe, a person may be forced to leave the workforce altogether. All of these scenarios translate to lost income over the course of a lifetime.One study found that restrictions in work often affect individuals with RA early in the course of the disease, with the use of disability benefits increasing sharply within 2 years of diagnosis. Another study that looked at the economic burden imposed by RA and osteoarthritis found that patients with RA had significantly higher expenses in terms of home care, child care, use of medical equipment and devices, and home remodeling than people without the disease. Patients with RA also had a significantly higher economic burden than patients with osteoarthritis and were 3 times more likely to have had a reduction in household income. Compared with osteoarthritis patients, individuals with RA had a greater reduction in work hours and a greater likelihood of having lost a job or taken early retirement. Additionally, a significantly higher percentage of RA patients in the study were unable to find work because of their condition compared with both osteoarthritis patients and people without either disease. Genetic factors Genetic factors account for 50% of the risk for developing RA. About 60% of RA patients in the United States carry a shared epitope of the human leukocyte antigen (HLA)DR4 cluster, which constitutes one of the peptide-binding sites of certain HLA-DR molecules associated with RA (eg, HLA-DR beta *0401, 0404, or 0405); HLA-DR1 (HLA-DR beta *0101) also carries this shared epitope and confers risk, particularly in certain southern European areas. Other HLA-DR4 molecules (eg, HLA-DR beta *0402) lack this epitope and do not confer this risk. Genes other than those of the major histocompatibility complex (MHC) are also involved, and results from sequencing genes of families with RA suggest the presence of several resistance and susceptibility genes, including PTPN22 and TRAF5. Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis (JRA), is a heterogeneous group of diseases that differs markedly from adult RA. JIA is known to have genetically complex traits in which multiple genes are important for disease onset and manifestations, and it is characterized by arthritis that begins before the age of 16 years, persists for more than 6 weeks, and is of unknown origin. The IL2RA/CD25 gene has been implicated as a JIA susceptibility locus, as has the VTCN1 gene. Some investigators suggest that the future of treatment and understanding of RA may be based on imprinting and epigenetics. RA is significantly more prevalent in women than in men, which suggests that genomic imprinting from parents participates in its expression. Imprinting is characterized by differential methylation of chromosomes by the parent of origin, resulting in differential expression of maternal over paternal genes. Epigenetics is the change in DNA expression that is due to environmentally induced methylation and not to a change in DNA structure. Clearly, the research focus will be on environmental factors in combination with immune genetics. Infectious agents For many decades, numerous infectious agents have been suggested as potential causes of RA, including Mycoplasma organisms, Epstein-Barr virus (EBV), and rubella virus. This suggestion is indirectly supported by the following evidence: Occasional reports of flulike disorders preceding the start of arthritis The inducibility of arthritis in experimental animals with different bacteria or bacterial products (eg, streptococcal cell walls) The presence of bacterial products, including bacterial RNA, in patients’ joints The activity of several agents that have antimicrobial effects as disease-modifying drugs (eg, gold salts, antimalarial agents, and minocycline) Emerging evidence also points to an association between RA and periodontopathic bacteria. For example, the synovial fluid of RA patients has been found to contain high levels of oral anaerobic bacterial antibodies common in periodontal infection, including Porphyromonas gingivalis. Pathogenesis RA is characterized not only by local inflammation damaging small and medium-sized joints but also by systemic inflammation. Different autoimmune and inflammatory processes are variably active in RA, making the entire disease entity clinically and pathobiologically heterogeneous. The e common denominators of differing RA subsets, such as autoimmunity and inflammation, are of key interest. Synovial Immunologic Processes and Inflammation Synovitis occurs when leukocytes infi