The
alkaloid fraction of Radix Linderae, the main active component of this herb
drug, has been proven to exhibit anti-inflammatory,
analgesic and antimicrobial activities. The present study was undertaken to investigate the therapeutic potential of
norisoboldine, the major
isoquinoline alkaloid present in Radix Linderae, in
collagen II -induced
arthritis (CIA) of mice as well as the possible mechanisms. CIA was induced in mice by immunization with chicken
type II collagen (II). After boosted on day 21, mice were treated with
norisoboldine (10, 20, 40 mg/kg) for twenty consecutive days. The clinical scores,
body weight changes and joint histopathology were evaluated.
Norisoboldine treatment significantly alleviated the severity of the disease, based on the reduced clinical scores and elevated the lowered
body weights of model mice. Meanwhile, this
alkaloid dose-dependently reduced the infiltration of inflammatory cells, synovial
hyperplasia and protected joint from destruction. Additionally, the serum level of anti-CII
IgG and the CII-stimulated lymphocyte proliferation were remarkably decreased in the groups administered with
norisoboldine. An assessment of Th1 function using the delayed-type
hypersensitivity model confirmed that
norisoboldine also significantly suppressed the enhanced T cell responses in vivo. These findings suggest that
norisoboldine might be a potential therapeutic agent for
rheumatoid arthritis, and it functions through protecting joint destruction as well as regulating the abnormal immune responses.