Prazosin, a selective
α1 adrenergic receptor antagonist,
with documented anti-inflammatory potential, was evaluated for its
antiarthritic efficacy by targeting specifically TNF-α. The
antiarthritic attribute of prazosin validated through in vitro screening comprised thermally provoked denaturation of bovine serum
albumin (BSA) and egg albumin along with membrane stabilization evaluation
at a concentration of 100–6400 μg/mL, while in vivo screening comprised
formaldehyde-instigated arthritis at the doses of 5, 10, and 20 mg/kg
and complete Freund’s adjuvant (CFA)-induced arthritis at 20
mg/kg dose. Paw swelling, body weight, arthritic score, hematological
parameters, and histological and radiographic examination of ankle
joints were assessed for a period of 28 days after CFA immunization.
Moreover, the proinflammatory cytokine TNF-α level was also
assessed through quantitative real-time polymerase chain reaction
(RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Prazosin revealed
significant antiarthritic effect evident through protein denaturation
inhibition in the egg albumin and the BSA model, stabilization of
red blood cell membrane in the membrane stabilizing assay, and reduction
in paw volume in formaldehyde-induced arthritis. Likewise, prazosin
exhibited propitious antiarthritic effects in the CFA-provoked arthritis
model manifested by paw volume and arthritic score alleviation, substantial
weight loss prevention, and preservation of the normal hematological
and biochemical profile. Histological and X-ray investigation unveiled
no substantive structural alterations in treated rat’s ankle
joints. The TNF-α expression level was also reduced. Thus, the
current study is suggestive that prazosin exhibits a strong antiarthritic
potential possibly through inhibition of TNF-α.