Honokiol protects against epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overproduction in rats post-laminectomy

Epidural fibrosis (EF)-induced failed back surgery syndrome (FBSS) in patients post-laminectomy remains a medical challenge. Although the scarring mechanisms remain unclear, the majority of aetiological studies have reported fibroblast dysfunction. Honokiol, the major bioactive constituent of the magnolia tree, exerts a variety of pharmacological effects, including anti-proliferative and anti-fibrotic effects, on various cell types. The present study investigated whether honokiol attenuates EF progression. In vitro, it was found that honokiol inhibited excessive fibroblast proliferation induced by transforming growth factor-β1 (TGF-β1) and the synthesis of extracellular matrix (ECM) components, including fibro-nectin and type I collagen, in a dose-dependent manner. These effects were attributed to the ability of honokiol to suppress the activity of connective tissue growth factor (CTGF), which is indispensable for the progression of fibrosis. Mechanistically, honokiol attenuated the TGF-β1-induced activation of the Smad2/3 and mitogen-activated protein kinase (MAPK) signalling pathways in fibroblasts. In vivo, honokiol reduced the proliferation of fibroblasts and the synthesis of ECM components, thus ameliorating EF in a rat model post-laminectomy. Taken together, these preclinical findings suggest that honokiol deserves further consideration as a candidate therapeutic agent for EF.