The Lignan-Rich Fraction from Sambucus williamsii Hance Exerts Bone Protective Effects via Altering Circulating Serotonin and Gut Microbiota in Rats

Abstract

Our previous study revealed that the bone anabolic effects of the lignan-rich fraction (SWCA) from Sambucus williamsii Hance was involved in modulating the metabolism of tryptophan in vivo and inhibiting serotonin (5-HT) synthesis in vitro. This study aimed to determine how SWCA modulates bone metabolism via serotonin in vivo. The effects of SWCA were evaluated by using 4-month-old Sprague-Dawley (SD) ovariectomized rats. The serum levels of 5-HT and kynurenine, the protein expressions of tryptophan hydroxylase 1 (TPH-1) and TPH-2, the genes and proteins related to the 5-HT signaling pathway as well as gut microbiota composition were determined. SWCA treatment alleviated bone loss and decreased serum levels of serotonin, which was negatively related to bone mineral density (BMD) in rats. It suppressed the protein expression of TPH-1 in the colon, and reversed the gene and protein expressions of FOXO1 and ATF4 in the femur in OVX rats, while it did not affect the TPH-2 protein expression in the cortex. SWCA treatment escalated the relative abundance of Antinobacteria and modulated several genera relating to BMD. These findings verified that the bone protective effects of lignans were mediated by serotonin, and provided evidence that lignans might be a good source of TPH-1 inhibitors.

Plasma serotonin precursors and metabolite are correlated with bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis

“…A previous study has documented that serum 5-HT level is inversely associated with BMD in rats. 30 In women, decreased BMD is correlated with serotonergic antidepressant use. 31 Patients suffering from neuroendocrine tumors have decreased hip BMD and increased urinary 5-HIAA.…”

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

“…The analysis of serotonin, kynurenine (Kyn), their respective isotopologs (D 4 -serotonin, D4-L-Kyn), and internal standard (IS, 5-Methoxytryptamine) was performed on an ACQUITYTM UPLC system (Waters Corp., Milford, CT, USA) coupled to a Xevo TQ-XS mass spectrometer (Waters Corp.), as described in our previous study [7] .…”

“…Cell culture and MTS assay RBL2H3 cells were purchased from Procell (Wuhan, China) and cultured routinely in the medium and under the conditions described in our previous study [7] . Cells were seeded at a density of 1 × 10 4 and 5 × 10 4 cells per well in 96-well plates and 24-well plates, respectively.…”

“…It is a traditional fork medicine used to treat bone fractures and joint-associated diseases [3] . Our previous studies demonstrated the beneficial effects of the lignan-rich fraction of S. williamsii on estrogen deficiency-induced bone loss [4][5][6] and revealed that these actions were mediated by suppressing the synthesis of gut-derived serotonin through inhibition of intestinal tryptophan hydroxylase 1 (TPH-1) [7] .…”

Plant-Derived Bioactive Compounds and Potential Health Benefits: Involvement of the Gut Microbiota and Its Metabolic Activity

“…5.1.39BFAA was negatively correlated with the level of enterolactone. In a study on rats, Xiao et al [ 84 ] showed that lignans mainly escalated the abundance of Antinobacteria and modulated several genera relating to bone mineral density, achieving the effect of alleviated bone loss and decreased serum levels of serotonin.…”