Evaluation of Pharmacological Components and Potential Targets of Thymus serpyllum in the Treatment of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis is autoimmune disorder that cause inflammation of joints and it result in destruction of cartilage and joints. The exact etiology is unknown although it is believed that it results when genetic an environmental cause the modification in our own antigen. According to WHO, it is affecting 0.3-1% of world‟s population. In Pakistan, its prevalence is 0.5-1.9%. Women are affecting three times more than man. Current treatment includes NSAIDs and DMARDS which alleviate the inflammation and reduces pain in joints. But their adverse side effects have limited their use. So scientific community is trying its alternative to use herbal plants as medicine to treat the RA because they have minimum side effects, non-toxic have phytochemical that have therapeutic potential and are cost effective. Bioactive plants and various compounds extracted from them have anti-inflammatory and anti oxidant role, has been previously reported. Thymus serpyllum is present around the world on rocky slopes at high altitude. In Pakistan, it naturally grows in Gilgit Baltistan and according to New York Botany Garden, it accession number is 3705/94*A. The leaves of this plant has the therapeutic potential henceforth the objective of the study was to evaluation of pharmacological components and potential targets of Thymus serpyllum in the treatment of Rheumatoid arthritis. Aqueous and methanol extract were found positive for various bioactive phytochemicals like phenols, flavonoids, di-terpenes, tannins, terpenoid, anthraquinones and glycosides. Extract exhibit good anti-oxidant activity assessed by DPPH assay and H202 scavenging assay. It also displayed significant anti-inflammatory activity assessed by Percentage inhibition of albumin denaturation assay. BALB/C collagen induce arthritis mice model was designed characterized by histopathological, clinical chemistry testing and Catalase assay to achieve objective of the study. T. serpyllum treated mice extract exhibit notable reduction in paw size. Liver and kidney enzymes had shown normal parameters ranges which indicated that mice were recovering from XVIII Evaluation of Pharmacological Components and Potential Targets of Thymus serpyllum in the Treatment of Rheumatoid Arthritis arthritis after treatment with Thymus serpyllum. Histopathology results of ankle joints had also displayed mice with T. serpyllum administration had shown reduction in inflammation of joints. In-silico study design shown that eight compounds out of 233 in T. serpyllum have drug-like potential. Network pharmacological analysis had shown that there are certain protein that are present in RA and as well as in eight shortlisted compounds. The predicted targets have role in inflammatory pathways like JAK-STAT growth hormones receptor signaling pathway, IL-17 signaling pathway, and Rheumatoid arthritis and Relaxin pathway. Enrichment analysis results further shortlisted the proteins which have role in signaling pathways i.e. JAK3, JAK2, STAT3 and MAPK1. Docking analysis of four proteins with eight compounds had displayed promising results. The docking score obtained shown that compound 2H-3,5a-Epoxynaphth (2,1)-boxepin, shown lowest binding energy with JAK3, STAT3, JAK2 and MAPK1. This lowest binding energy indicated that compound needed minimum energy to interact with proteins and made more stable ligand-target complex. Our current study has concluded that that T.serpyllum have anti-inflammatory and anti-oxidant potential in relieving the manifestation of disease. T.serpyllum compounds have potential to target the proteins involved in Arthritis. However, additional in-vitro and in-vivo is highly recommended to evaluate efficacy of eight compounds in ameliorating the effects Rheumatoid arthritis progression.