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.