Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment

Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation. Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance, a folk herbal medicine used to treat bone fractures and joint diseases in China, exerted bone-protective effects, and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1 (TPH-1). However, there is no direct evidence for the action of lignans on TPH-1. This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties. Molecular docking, surface plasmon resonance, TPH-1 protein activity, TPH-1 protein expression, mouse serum serotonin levels, and bone properties upon lignan treatment were determined. This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases, including osteoporosis.