Pharmacological support to anti-arthritic prospective of physostigmine: a new approach

Inflammopharmacology. 2021 Aug;29(4):1119-1129. doi: 10.1007/s10787-021-00840-9. Epub 2021 Jul 5.

Abstract

Rheumatoid arthritis (RA) is a slowly progressing inflammatory autoimmune disease. Several features are involved in the RA pathogenesis in addition to environmental and genetic factors. Previously it has been reported that acetyl cholinesterase (AChE) activity is enhanced in old age and may contribute in the progression of RA. The current experimental work was projected to assess the activity of physostigmine (a cholinesterase inhibitor) for treatment of RA. In vitro and in vivo approaches were used for such evaluation. However, enzyme linked immunosorbent assays (ELISA) was performed to determine the concentrations of Prostaglandins E2 (PGE2) and tumor necrosis factor-α in arthritic rats after treatment with physostigmine. Moreover, anti-oxidant assays were employed to calculate the level of super oxide dismutase (SOD) and catalase peroxidase (CAT) in tissue of treated animals. The results claimed the dose dependent protective and stabilizing effect of physostigmine on denaturation of albumin (egg and bovine serum) protein and human red blood cell membrane, respectively, through in vitro studies. Furthermore, the physostigmine (10 and 20 mg/kg) significantly (p < 0.001) reduced the swelling of paw after induction of arthritis with formaldehyde or complete Freund's adjuvant (CFA) as compared to arthritic control animals. Moreover, significant (p < 0.001) reduction in the levels of inflammatory markers (PGE2 and TNF-α) at doses of 10 and 20 mg/kg of physostigmine has been observed in ELISA test. Likewise, there was a prominent rise in levels of SOD and CAT in animals treated with physostigmine. These findings pharmacologically conclude the anti-arthritic effect of physostigmine.

Keywords: Bovine serum albumin; NSAIDs; PGE2; Physostigmine; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology*
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Humans
  • Male
  • Physostigmine / pharmacology*
  • Physostigmine / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / antagonists & inhibitors
  • Serum Albumin, Bovine / metabolism

Substances

  • Antirheumatic Agents
  • Cholinesterase Inhibitors
  • Serum Albumin, Bovine
  • Physostigmine