1 research outputs found
Pyrano-isochromanones as IL‑6 Inhibitors: Synthesis, in Vitro and in Vivo Antiarthritic Activity
Bergenin (<b>1</b>), a unique
fused <i>C</i>-glycoside
isolated from Bergenia species, possesses
interesting anti-inflammatory and antipain activities. To study SAR
of this scaffold, first-generation derivatives were synthesized and
evaluated for inhibition of lymphocyte proliferation and production
of pro-inflammatory cytokines. The C-7 substituted derivatives showed
inhibition of IL-6 as well as TNF-α production. Bergenin and
its most potent IL-6 inhibitor derivatives <b>4e</b> and <b>4f</b> were then investigated in a panel of in vitro and in vivo
inflammation/arthritis models. These compounds significantly decreased
the expression of NF-kB and IKK-β in THP-1 cells. In in vivo
study in BALB/c mice, a dose-dependent inhibition of SRBC-induced
cytokines, reduction in humoral/cell-mediated immunity, and antibody
titer was observed. The CIA study in DBA/1J mice indicated that compounds
led to reduction in swelling of paws, cytokine levels, and anticollagen
IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy
of pyrano-isochromanones demonstrates the promise of this scaffold
for development of next-generation antiarthritic drugs