Formulation development of anti-rheumatoid gel of Saraca asoca (Roxb. ) De Wilde hydroalcoholic extract containing eucalyptus oil and peppermint oil as penetration enhancer

Abstract In the present research investigation, various concentrations of hydro-alcoholic extract of Saraca asoca (Roxb.) De Wilde (family: Caesalpinaceae) dried bark and carbopol polymer at different temperature ranges were optimized for the preparation of gel formulation. Natural penetration enhancers, v.i.z., eucalyptus oil and peppermint oil were incorporated separately in the extract based gel formulations to study the rate of drug permeation across egg membrane, using franz diffusion cell. In vitro anti-arthritis potential of the formulations was also studied using inhibition of albumin denaturation, antiproteinase activity and membrane stabilization method. As per the results of current study, it is established that S. asoca dried bark hydroalcoholic extract based gel prepared using peppermint oil as penetration enhancer exhibited good permeation rate of 8.48% at the end of 3 h. The percentage inhibition of proteins by antiproteinase method at concentration of 50 µg/ml was 50.01±1.00% which was close to 53.92±0.99% as shown by the standard drug, Diclofenac. Also, the percent protein inhibition determined using membrane stabilization method was found to be 49.70±1.00%, however, it was 63.32±0.94% for the standard drug, Diclofenac. Hence, it is concluded that peppermint oil may act as a good candidate for the preparation of potent anti-rheumatic gel preparations.

SUMO-conjugating enzyme UBC9 promotes proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with high morbidity and mortality. Fibroblast-like synoviocytes (FLS) in the synovial tissues play critical roles in joint destruction. Recent studies implicate the sumoylation in the regulation of the inflammation and arthritis. Thus, we explored whether SUMO-conjugating enzyme UBC9 is involved in the progression of RA using a mouse collagen-induced arthritis (CIA) model. The effects of UBC9 siRNA on cell invasion and migration in human RA-FLS were also assessed in vitro. Treatment with siRNA against UBC9 for 3 weeks reduced the arthritis score and joint destruction. The expression of SUMO-1 and UBC9 protein in CIA joints was inhibited by UBC9 knockdown. Serum levels of anti-collagen (CII) antibodies, vascular endothelial growth factor A (VEGF-A), matrix metalloproteinases (MMP)-3, and MMP-9 were also decreased in CIA mice. In vitro, UBC9 silencing inhibited the secretion of VEGF-A, MMP-3, and MMP-9 from TNF-α-stimulated human RA-FLS. TNF-α-induced RA-FLS proliferation and migration were significantly attenuated by UBC9 knockdown. These findings indicate that SUMO-conjugating enzyme UBC9 promotes proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis. Inhibition of UBC9 activity may be a viable therapeutic target in amelioration of disease progression in RA by attenuating FLS proliferation, migration, and invasion.