Investigation of Therapeutic Potential of Thymus serpyllum on Inflammation and Autophagy in Collagen Induced Arthritic Mice

Abstract

Rheumatoid Arthritis (RA) is a systemic autoimmune disorder that affects approximately 1% of the world population and characterized by bone erosion, cartilage degradation, synovial hyperplasia, inflammatory and fibroblast like synoviocytes (FLS) infiltration. In rheumatoid arthritis, macroautophagy has been observed to be elevated which complicates its pathogenesis and treatment. As resistance to current treatment options is a major concern with disruption of autophagy being as one of the primary reasons to the resistance, to shed light on this phenomenon, current study has been carried out. Tomorou, Thymus serpyllum, is an indigenous ethnobotanical medicinal plant from HunzaNagar Valley and used against inflammatory problems. In the given study, antiinflammatory and anti-rheumatic effect of ‘tomoru’ to unravel the underlying mechanism of RA has been evaluated. The results demonstrate that the aqueous and ethyl acetate extracts of tomoru had anti-inflammatory effect as IL6 levels were lowered after their administration to the Collagen Induced Arthritic (CIA) Mice Model. A distinctive pattern in the expression of autophagy and apoptotic markers was observed that indicated that autophagy in RA is via ULK1 independent non-canonical pathway. The extract administration alleviated the symptoms of RA either through induction of ULK-1 dependent pathway or apoptosis induction. Results of immunohistochemistry and scanning electron microscopy of muscle has showed activity tomoru against autophagy while histopathology of ankle and tarsal joints has depicted retention of joint architecture in CIA mice model. This understanding in autophagy in RA has contributed to better disease control and management.