title: WIN-34B May Have Analgesic and Anti-Inflammatory Effects by Reducing the Production of Pro-Inflammatory Mediators in Cells via Inhibition of IκB Signaling Pathways.
abstract: WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, PGE2, and MMP-13 in IL-1β-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of PGE2, NO, IL-1β, and TNF-α were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and PGE2 was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. IκB signaling pathways were inhibited by WIN-34B, and the migration of NF-κB into the nucleus was inhibited, which is consistent with the degradation of IκB-α. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators.
authors.affiliation: East-West Bone & Joint Research Institute.
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Choi
authors.forename: Hyung-In
authors.initials: HI
authors.lastname: Yang
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Yoo
keywords: Analgesic effect; Anemarrhena asphodeloides BUNGE; Anti-inflammatory effect; Lonicera japonica Thunb; WIN-34B