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

Abstract

Objective: 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.
Methods: Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1. The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells. The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.
Result: The lignans showed high binding scores and binding affinities to TPH-1, inhibited the activity and protein expression of TPH-1, suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.
Conclusion: 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.

Keywords

Lignan / Osteoporosis / Sambucus williamsii Hance / Serotonin / TPH-1 inhibitor

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This work was supported by the Natural Science Foundation of Guangdong Province (2021A1515010648), the National Natural Science Foundation of China (81903616), The Hong Kong Polytechnic University Start-up Funding (A0038607), The Mainland-Hong Kong Joint Funding Scheme (ITF-MOST: MHX/002/20).

Author contributions

Yu-Xin Zhu and Lu Lu conducted the research and investigation process, specifically performed the in vitro and in vivo experiments, respectively, and Yu-Xin Zhu and Zi-Ling Tang wrote the manuscript. Dabo Pan and Yang Yu performed the docking experiments and analyzed the results. Zi-Ling Tang and Zuo-Cheng Qiu carried out the SPR analysis and did the analysis. Hui-Hui Xiao supervised the whole research activities. Man-Sau Wong and Hui-Hui Xiao acquired the funding and edited the manuscript.

Ethical approval of studies and informed consent

All animal procedures were ethically approved by the Ethics Committee of the Hong Kong Polytechnic University Animal Subjects (ASEC Case: 180402).

Acknowledgments

We thank Ms. Leung Hong-Man for the language polishing, the technical writer of The Hong Kong Polytechnic University.

Data availability

All data generated or analyzed during this study are included in this published article.

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Acupuncture and Herbal Medicine