Rheumatoid arthritis (RA) is a life-long autoimmune illness characterized by chronic inflammation that causing joint pain and destroying cartilage and bone [1]. 1–3 % of the population is affected with this disorder all over the globe. Women over the age of 55 are 2–3 times more prone than men to Rheumatoid Arthritis. RA is symptomized by swelling, persisting pain, stiffness, Tenderness and flares or excaherbation especially in synovial joints (Knee, Shoulders, Elbows, Wrist, knuckles and feet) in the body. Synovial joints are present as a connection between the bones/cartilage that move against each other; normally 1–3 cells thick layer present at the site of synovial joint where synovial cavity is found. Synovial cavity is filled with a thick, dense, and viscous fluid known as Synovia or synovial fluid, that acts as a lubricant in bones friction or movement [7].
Synovial membrane or layer is hypertrophied in RA, and layer becomes (8–10 cells) thick joint space reduces because of that [2]. In this disorder, synovial area is heavily penetrated with own immune cells and inflammatory cells including lymphocytes (T and B cells) neutrophils, mast cells, eosinophils, and macrophages). New blood vessels are formed near the inflamed area. Because of this auto-immune mechanism, cartilage and bones are destroyed and eroded by the hypertrophied synovium and it leads deformity and dysfunction of bones and cartilage [8]. No permanent treatment is available, although many disease-modifying anti-rheumatic drugs (DMARDs), steroidal drugs, and non-steroidal anti-inflammatory drugs are available in the market with severe to low side -effects and high cost [9].
India and its neighbouring countries (China,Bangladesh,Nepal and sri Lanka) have been using plants since ages for its surprising medicinal properties and therapeutic effects[3]. And “Withania somnifera” is one of the most used medicinal plants in India, Sri-Lanka and Bangladesh for its therapeutic potential. Withania somnifera is also known as the Indian Ginseng in local language and Ashwagandha in Hindi. It belongs to the family Solanaceae and found in hot and dried region areas. It is a shrub plant [10]. And has many medicinal properties including Anti-inflammatory, Anti-bacterial, Aphrodisiac, Anti-cancer, Adaptogenic, Anti-depression, and Anti-stress properties. Dried roots have been using for therapeutic use, studies show that leaves also have medicinal effects [4]. This plant has many phyto-compounds including Phenolics, Alkaloids, Steroidal and other compounds [5]. The disease “Rheumatoid Arthritis” is characterized by Inflammation and several cytokine pathways I/II on the molecular level [6]. So, we chose this Withania’s 18 compounds for its anti-inflammatory potential as ligands. And Interleukin-6(IL6) and JAK3 as the target proteins involved in Rheumatoid Arthritis Pathogenesis. So, we used 18 ligands for molecular docking (This is a blind docking) against IL6 and JAK3 targets in Rheumatoid Arthritis.